Sinusitis is an inflammation of the paranasal sinuses typically associated with an upper respiratory infection. Sinusitis is this country's most common health-care complaint, affecting an estimated 31 million people. (A. Moss and V. Parsons, National Center for Health Statistics, 1986: 66-7, DHHS Publication No. (PHS)86-1588 (1985)). Other less common causes include allergies, air pollution, diving and swimming under water, structural defects of the nose (deviated septum), and as a complication of dental work. A common complication of sinusitis is a related middle ear infection (otitis media) due to the close proximity of the sinuses and eustachian tube. (M. Revonta and A. Blokmanis, Can. Fam. Physician 40, 1969-72, 1975-76 (1994)). In addition, most patients with primary ciliary diskinesia experience chronic or recurrent episodes of sinusitis.
As the sinus inflammation progresses, mucus from the sinuses becomes trapped within the sinus passages. This blockage of mucus contributes to the headache, pain, fever, and difficulty in breathing commonly reported in this disorder. Common symptoms are headache, tenderness or discomfort over the forehead and sinus area of the face, nasal discharge, slight increase in temperature, and general malaise.
At the present time, current treatment for sinusitis consists of antibiotics for the infection, antihistamine/decongestant agents (typically nasal spray or drops) or saline nasal sprays to relieve congestion, mucolytic agents, steam inhalation, warm compresses applied over the sinus area, analgesics, and anti-inflammatory agents to relieve discomfort. (D. Kennedy, Otolaryngol. Head Neck Surg. 103, 845-46 (1990)). In addition, exposure to environmental irritants, such as pollution, smoke, and dust should be eliminated or reduced. If the sinusitis becomes a chronic problem, surgical enlargement and drainage of the sinus passages may be considered.
An additional patient population at risk for development of sinusitis is patients who are intubated with a nasotracheal tube. (J. Reuler, West J. Med. 163(1), 40-8 (1995)). The tube irritates the lining of the nasopharyngeal airways, and because of the close proximity to the sinuses and the large number of microorganisms present in the nasopharyngeal airways, severe sinusitis may result. At present, treatment measures remain similar to those described above, including antibiotics, analgesics, warm compresses, and surgical drainage, but also require removal of the nasotracheal tube and reintubation by tracheostomy, or, in fewer cases, by the oropharyngeal route. The symptoms of this type of sinusitis are intense discomfort and tenderness over the sinus area, increased drainage from the naso-sinus airways, fever, and potentially other, more severe infections and complications.
Uridine 5'-triphosphate (UTP) and adenosine 5'-triphosphate (ATP) have been shown to affect the ion transport activity of human airway epithelial cells, as described in U.S. Pat. No. 5,292,498. Specifically, UTP and ATP induce chloride and water secretion in the lung epithelial cells of cystic fibrosis patients, helping to liquify and facilitate transport of the highly viscous airway surface mucus that characterizes this disease. It has also been found that UTP and ATP stimulate the ciliary beat frequency in lung epithelial cells, further facilitating the transport of mucus from the lungs of cystic fibrosis patients, pneumonia patients, or normal individuals. (R. Boucher, et al., Adenosine and Adenine Nucleotides: From Molecular Biology to Integrative Physiology, p. 525-32 entitled "Mechanisms and Therapeutic Actions of Uridine Triphosphates in the Lung" (L. Belardinelli, et al. ed., Alumwer Academic Publishers, Boston 1995); (L. Gheber, et al. J. Membrane Biol. 147, 83-93 (1995)). A French biotechnology company, Laboratoires SYNTHELABO FRANCE, has developed a method of treating nasal mucous fluid congestion under the trademark name rhinATP.TM. which uses adenosine triphosphate (ATP) as the active compound. This technology for rhinATP.TM. was licensed under U.S. Pat. No. 5,420,116 (applicant intends the disclosure of this and all other patent references and publications cited herein be incorporated herein by reference). Their method of treatment comprises administering ATP to the nasal cavity via nasal spray or nasal drops.
Applicant has discovered that the clearance of the retained mucous fluid in sinusitis patients can be facilitated by administering UTP and its related compounds as well as other nucleoside phosphates such as: P.sup.1,P.sup.4 -di(uridine-5') tetraphosphate (U.sub.2 P.sub.4); adenosine 5'-triphosphate (ATP); cytidine 5'-triphosphate (CTP); 1,N.sup.6 -ethenoadenosine 5'-triphosphate; adenosine 1-oxide 5'-triphosphate; 3,N.sup.4 -ethenocytidine 5'-triphosphate; or P.sup.1,P.sup.4 -di(adenosine5') tetraphosphate (A.sub.2 P.sub.4) to the site of fluid blockage. UTP and U.sub.2 P.sub.4 are the preferred embodiments of the present invention. By administering UTP or U.sub.2 P.sub.4 soon after symptoms first appear, total blockage of the sinuses and the resulting symptoms may be avoided.